On a global basis, tropical infectious diseases take an enormous human toll, particularly affecting the poor and dispossessed. The candidate, an Associate Professor of Medicine with tenure, proposes a multifaceted mentoring and career development plan in patient-oriented research towards expanding research capacity in tropical infectious diseases and contributing to the improvement of global public health. This plan will build on the candidate's established strengths in malaria and leptospirosis field research in the developing country setting and provide opportunities for junior physician scientists to obtain formal training in tropical infectious disease research. The K24 award will protect the candidate's time to allow him to continue devoting more than 90% of his professional effort to research and mentoring. This program will include: one-on-one mentoring of junior physician scholars ('including medical students, MSTP students, internal medicine residents in a new global health track, infectious disease clinical fellows and junior clinical faculty members), the formal participation of the candidate in expanding UCSD's K30-funded clinical research training program to include training in international health and global infectious diseases; and professional development for the candidate to allow him to incorporate new skills into his research. The candidate proposes to obtain formal, mentored training in statistical genetics and systems biology to allow him to study genetic predisposition to infectious disease outcomes. Dr. Vinetz's ongoing patient-oriented research on malaria and leptospirosis will serve as research vehicles. His malaria research focuses on: 1) using molecular epidemiological approaches to delineate human reservoirs of malaria transmission, towards the design and deployment of novel approaches to malaria control; and 2) determining mechanisms of naturally acquired transmission-blocking immunity in the Peruvian Amazon population. His patient-oriented research in leptospirosis focuses on: 1) determining zoonotic reservoirs of leptospirosis transmission to humans; 2) delineating anthropogenic influences on the environment that lead to human leptospirosis; and 3) determining host genetic determinants of the outcome of leptospiral infection. The K24 award will allow the candidate to continue and augment his successful patient-oriented research programs and provide the intellectual environment needed to increase the number of physician-scientists capable of carrying out cutting edge patient-oriented research in tropical infectious diseases and global health.